LIVER PATHOLOGY(3) Prof. Andras Kiss. M.D., Ph.D., D.Sc. Semmelweis University 2 nd Department of Pathology Budapest February 26.
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1 LIVER PATHOLOGY(3) Prof. Andras Kiss. M.D., Ph.D., D.Sc. Semmelweis University 2 nd Department of Pathology Budapest February Vascular disorders Inflow A.hepatica thromb., embolia infarctus V.portae obstruction, thrombosis (pylethrombosis) portal hypertension, causes Trough congestion, hepar moschatum, peliosis hepatis Outflow Budd-Chiari syndrome VOD 1
2 Budd-Chiari syndrome (Extended hemorrhages in the liver parenchyma caused by thrombosis of hepatic veins) Nemesánszky-Schaff-Szalay Hepatologia Oktató CD 2004 Falk 2
3 Liver alterations associated with pregnancy Acute steatosis in pregnancy rare, from mild to severe (could be fatal), 3.trimester, perinatal, microvesicular steatosis, pancreatitis (common) Intrahepatic cholestasis in pregnancy 3. trimester, icterus, iching, cholestasis,?? Praeeclampsy, eclampsy HELLP-syndrom (hemolysis, elevated liver enzymes, low platelets), pale liver with red foci, fibrin deposits in sinusoids, hemorrhages 3
4 LIVER PATHOLOGY (3) Focal liver lesions Benign tumors and tumor-like lesions Malignant tumors Liver transplantation Diseases of gallbladder and bile ducts Diseases of gall bladder Diseases of extrahepatic bile ducts Tumors (**)= important, ( ), not for exam (extra)!!! Focal liver lesions (**) Tumor-like lesions of the liver FNH, NRH, mesenchymal hamartoma, cysts, inflammatory pseudotumor, abscessus, infarctus Benign liver tumors Non epithelial: haemangioma, fibroma, angiomyolipoma etc Epithelial: adenoma (HCA, CCA) Malignant liver tumors Non epithelial: haemangiosarcoma, -endothelioma embryonal sarcoma, lymphoma Epithelial: hepatocellular cc, cholangiocellular cc., mixed, hepatoblasoma 4
5 Classification of liver cysts (1) ( ) I. Parasitic II. Non parasitic A. Soliter B. Hereditary 1. Non-communitating ductal 2. DPM ( ductal plate malformation - communitating) CHF (cong. hepatic fibrosis) ARPKD syndromes (Meckel-Gruber, Ivemark) 3. Isolated hepatic *Witzleben, G. L., Ruchelli, E. Classification of liver cysts (2) ( ) II. Non parasitic C. Systemic biliary dilatative 1. Without choledochus cyst ( simple Caroli disease) 2. With choledochus cyst D. Other 1. Traumatic, infarction 2. Duodenal duplication 3. Tumors with cyst cystadenoma/-carcinoma mesenchymal hamartoma giant cavernous haemangioma teratoma other 4. Peliosis *Witzleben, G. L., Ruchelli, E. 5
6 Ecchinococcus cyst Hepar polycysticum 1 cm 6
7 Mesenchymal hamartoma (children, benign) 1 cm Tumor-like focal liver lesions (**) Focal nodular hyperplasia (FNH) Inflammatoric pseudotumor Mesenchymal hamartoma Nodular regenerativ hyperplasia Infarct Granulomas (Boeck, tbc etc) 7
8 Focal nodular hyperplasia (FNH)(**) - Female predominance, - Well circumsized, - No capsule - Central scar (fibrous septa radiate, focal cirrhosis ) - Color (pale, fatty, haemorrhagic etc.) - Bile ducts: numerous, tortuous - Inflammatory cells -important!!! Focal Nodular Hyperplasia (FNH) (central scar!!!) 8
9 FNH 1 cm FNH 1 cm
10 Haemangioma hepatis (giant form) 10
11 1 cm 1 cm 11
12 Focal Nodular Hyperplasia (FNH) FibroLamellar hepatocellular Carcinoma (FLC) Focal Liver Lesions FNH HCA (prev. FNH teleang.) Hemang. FLC 12
13 Hepatocellular adenoma (HCA) (**) - Female predominance - Associated with oral contraceptives, anabolic steroids - Sharply demarcated, - Encapsulated - Homogenous structure, but hemorrhage, necrosis common, - Steatosis, no bile ducts in the tumor adenoma hepatocellulare (HCA) (yellow, steatosis, capsule) 13
14 HCA: Variant 3 teleangiectatic Monoclonal Dilated vessels Haemorrhagies Less or no steatosis Biliary vessels (less in number) 14
15 HCA Variant 3 10 cm 15
16 CK7 Classification of hepatocellular adenomas: association with HCC or borderline lesion Zucman-Rossi et al., Hepatology 2006;43;515 16
17 Adenoma hepatocellulare (extended bleeding, rupture might occur) 1 cm Hepatocellular carcinoma (**) - Cirrhosis (70%) - Association with HBV/HCV/alkohol etc - Gross: uneven border, usually no capsule, haemorrhage, necrosis - Hist: trabecular, pseudoglandular (acinar), clear cell, scirrhous, fibrolamellar (grades I-IV) - Progression: infiltration of capsule (if exists), venous invasion 17
18 HCC extracapsular HCC necrosis cirrhosis HCC 18
19 Fibrolamellar HCC 1 cm SCIENCE :
20 HCC cirrhosis cirrhosis HCC HCC, trabecular form Different histological types of HCC HCC, trabecular HCC, pseudoglandular HCC, venous invasion HCC, anaplastic 20
21 Staging of HCC TNM-Classification T1 solitary tumor without vascular invasion T2 solitary tumor with vascular invasion or multiple tumors < 5 cm diameter T3 multiple tumors > 5 cm diameter or tumor invasion of major veins T4 tumor(s) with invasion of adjacent organs or perforation of visceral peritoneum Stage Grouping Stage I T1 N0 M0 Stage II T2 N0 M0 Stage IIIA T3 N0 M0 Stage IIIB T4 N0 M0 Stage IIIC any T N1 M0 Stage IV any T any N M1 Therapeutic (surgery) relevance Llovet J.M., Bruix J. Hepatology :
22 Llovet J.M., Bruix J. Hepatology : Llovet J.M., Bruix J. Hepatology :
23 Angiogenesis and HCC Proangiogenic factors overexpressed in HCC: Vascular endothelial growth factor (VEGF) Platelet-derived growth factor (PDGF) Placental growth factor Transforming growth factor α and β Basic fibroblast growth factor Epidermal growth factor (EGF) Hepatocyte growth factor Angiopoietinek Interleukin (IL)-4, IL-8 Semela D, Dufour J-F. J Hepatol 2004;41: Characteristics of HCC 5% of malignant tumors new cases annually (in 2000) and similar death Incidence is dubbled in the past 20 yrs (Japan, USA, Sweden, France) 7. in males 9. in femels Characteristic geography Etiological factors: HBV, HCV, AFB1 (80%), alkohol etc Unknown 35% HBV/HDV 5% HBV 15% HCV 45% Koff RS, et al. Viral Hepatitis. 2nd ed
24 Metabolic diseases Androgens Hepatocarcinogenesis Etiological factors HCC Alcohol Mutagen effects Cirrhosis! Schistosoma HBV, HCV Aflatoxin Fusarium toxin Classification of tumors of bile ducts Cholangiocarcinoma (CC) intrahepatic CC perihilar CC (previously Klatskin tumor) distal (CC) 24
25 Cholangiocarcinoma. Perihilar CC 25
26 Cholangiocarcinoma. Tumor, protruding from the Liver Ductus choledocus 26
27 27
28 28
29 2014:1-12 Biliary hamartoma (von Meyenburg complex) 29
30 Biliary hamartoma (von Meyenburg complex) Gallbladder (**) 1. Tumorlike lesions - Inflammatory origin (polyp, xanthogranulomatous cholecystitis etc) - Hyperplasia (papillary, adenomyomatous) - Heterotopic tissue (pancreas, stomach, endocrin) - Other 30
31 Gallbladder (**) 2. Tumors Benign - adenoma - cystadenoma - papillomatosis - mesenchymal Malignant - epithelial - adenocarcinoma - adenosquamosus cc. - squamosus cc. - differenciálatlan - cystadenocarcinoma - mesenchymal - endocrin - carcinoid Gallbladder carcinoma (**) Gross - infiltrating - exophytic Histology - adenocarcinoma Other - TNM - occult carcinoma - in situ carcinoma Immunohistochem - CEA - CA
32 Gallbladder cc Adenocarcinoma Ductus choledochus carcinoma (CC, distal type) 32
33 Most common metastatic liver tumors (**) Gastrointestinal tract, gallbladder, bile ducts, pancreas Lung Kidney Breast Melanoma Neuroendocrin Metastatic liver tumors 33
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